IMPORTANCE: Advances in artificial intelligence (AI) must be matched by efforts to better understand and evaluate how AI performs across health care and biomedicine as well as develop appropriate regulatory frameworks. This Special Communication reviews the history of the US Food and Drug Administration's (FDA) regulation of AI
presents potential uses of AI in medical product development, clinical research, and clinical care
and presents concepts that merit consideration as the regulatory system adapts to AI's unique challenges. OBSERVATIONS: The FDA has authorized almost 1000 AI-enabled medical devices and has received hundreds of regulatory submissions for drugs that used AI in their discovery and development. Health AI regulation needs to be coordinated across all regulated industries, the US government, and with international organizations. Regulators will need to advance flexible mechanisms to keep up with the pace of change in AI across biomedicine and health care. Sponsors need to be transparent about and regulators need proficiency in evaluating the use of AI in premarket development. A life cycle management approach incorporating recurrent local postmarket performance monitoring should be central to health AI development. Special mechanisms to evaluate large language models and their uses are needed. Approaches are necessary to balance the needs of the entire spectrum of health ecosystem interests, from large firms to start-ups. The evaluation and regulatory system will need to focus on patient health outcomes to balance the use of AI for financial optimization for developers, payers, and health systems. CONCLUSIONS AND RELEVANCE: Strong oversight by the FDA protects the long-term success of industries by focusing on evaluation to advance regulated technologies that improve health. The FDA will continue to play a central role in ensuring safe, effective, and trustworthy AI tools to improve the lives of patients and clinicians alike. However, all involved entities will need to attend to AI with the rigor this transformative technology merits.